Emergence of X4 usage among HIV-1 subtype C: evidence for an evolving epidemic in South Africa

Abstract

This study investigated the genotype and phenotype of HIV-1 isolates of 20 South African AIDS patients. We found the highest percentage of CXCR4 usage among primary isolates, in which 30% efficiently utilized CXCR4 and exhibited the syncytium-inducing phenotype. Phylogenetic analysis of env confirmed that 19 of the 20 were subtype C, and syncytium-inducing viruses had genetic changes in the V3 loop, characteristic of CXCR4 usage. Results imply that the frequency of CXCR4-utilizing subtype C is increasing with time.

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

“…HAART-naive subjects described in Connell et al, 15 are not statistically significant ( p = 1.0). Patients described in both studies were recruited from Gauteng province.…”

“…21 Seclén et al 23 showed an overall concordance of 88% between PSSM and geno2pheno. Reanalysis of the Connell et al 15 data using the two algorithms showed 100% concordance of genotype with phenotype for PSSM sinsi and 95% with geno2pheno. Hence, based on concordant results from the two most widely used algorithms, a minimum of 29% of HAART-failing patients in our study had X4-utilizing viruses.…”

“…[10][11][12][13][14] However, an increase in the incidence of X4 and R5X4 emerging at the late stages of infection in subtype C individuals has been reported. 15 The introduction of entry inhibitors, such as the R5 antagonist maraviroc, as components of highly active antiretroviral therapy (HAART), has heightened interest of HIV-1 coreceptor usage because of the concern that preexisting X4 viruses may emerge in patients as a consequence of treatment, which necessitates tropism testing prior to treatment initiation.…”

“…The full length envelope glycoprotein was reverse transcriptase polymerase chain reaction (RT-PCR) amplified and sequenced (population based) on the ABI Prism 3730 (Applied Biosystems, Foster City, CA). 15,16 Sequence data were edited using the Sequencing Analysis V5.3.1 program (Applied Biosystems), and the complete env sequences were assembled and manually edited using Sequencher V5.1 (Genecodes, Ann Arbor, MI). The V3 loop region was extracted, nucleotide sequences were converted to amino acid sequences, and coreceptor utilization and viral tropism were predicted manually by assessing sequences for typical features of X4 viruses 15,16 and by using the two most widely used publicly available predictive algorithms for clinical samples, C-PSSM sinsi (http://indra.mullins.microbiol.washington.edu/webpssm/) and geno2pheno [coreceptor] (http://coreceptor.bioinf.…”

Dearth of full-length HIV-1 sequences obscures the true HIV-1 genetic subtypes distribution in sub-Saharan Africa

“…HIV-1 subtypes may exhibit phenotypic differences. Subtypes are believed to impact on tropism, with some studies associating increased CXCR4 usage with infections with subtype C (Johnston et al, 2003;Connell et al, 2008), and others finding decreased CXCR4 usage in subtype C infections (Bjorndal et al, 1997;Abebe et al, 1999;Peeters et al, 1999;Esbjornsson et al, 2010). Subtypes may have an important effect on transmission of HIV-1, as the subtype B was associated with homosexual transmission and the subtype C with heterosexual transmission (van Harmelen et al, 1997;van Harmelen et al, 2001), but a heterosexually driven subtype B epidemic has been observed in Trinidad and Tobago (Cleghorn et al, 2000).…”